Phenolate radical coupling as a method of triterpene synthesis

Author

Maehlum, Ellen Viggen

Date

1968

Advisor

Stevens, Robert V.

Degree

Master of Arts

Abstract

The dienone [B] is a possible precursor for the synthesis of tetra- and pentacyclic triterpenes. In this investigation a synthesis of the dimeric phenol [A] and the conversion of [A] to [B] by a phenolate radical coupling reaction is presented. The intermediate 5-hydroxy-o-toluic acid is prepared in two ways. The best method consists of heating 2-naphthol-6, 8-disulfonic acid dipotassium salt with sodium hydroxide in an autoclave. In the other method, o-xylene is treated with chlorosulfonic acid, and the resultant sulfonylchloride exposed to ammonium carbonate to yield the corresponding sulfonamide. Oxidation of the sulfonamide with potassium permanganate gives o-toluic acid-5-sulfonamide, which is fused with potassium hydroxide to yield 5-hydroxyotoluic acid. After protecting the phenol group, esterification and subsequent reduction with lithium aluminum hydride gives 2-methyl-5-methoxybenzyl alcohol. This alcohol is treated with phosphorus tribromide yielding the corresponding bromide which reacts with magnesium in the presence of ferric chloride to give a dimeric ether. The ether is finally converted to the dimeric phenol [A]. Several different oxidizing agents are tried to transfer the phenol [A] to the dienone [B]. No useful method is found for preparative work, but the dienone is obtained in poor yield by oxidation with manganese dioxide.